tbuckley/cabot-search huggingface dataset:
Transferability of Alzheimer Disease Polygenic Risk Score Across Populations and Its Association With Alzheimer Disease-Related Phenotypes
Authors: Sang-Hyuk Jung, Hang-Rai Kim, Min Young Chun, Hyemin Jang, Minyoung Cho, Beomsu Kim, Soyeon Kim, Jee Hyang Jeong, Soo Jin Yoon, Kyung Won Park, Eun-Joo Kim, Bora Yoon, Jae-Won Jang, Yeshin Kim, Jin Yong Hong, Seong Hye Choi, Young Noh, Ko Woon Kim, Si Eun Kim, Jin San Lee, Na-Yeon Jung, Juyoun Lee, Ae Young Lee, Byeong C. Kim, Soo Hyun Cho, Hanna Cho, Jong Hun Kim, Young Hee Jung, Dong Young Lee, Jae-Hong Lee, Eek-Sung Lee, Seung Joo Kim, So Young Moon, Sang Joon Son, Chang Hyung Hong, Jin-Sik Bae, Sunghoon Lee, Duk L. Na, Sang Won Seo, Carlos Cruchaga, Hee Jin Kim, Hong-Hee Won
Journal: JAMA Network Open (2022)

Importance Polygenic risk scores (PRSs), which aggregate the genetic effects of single-nucleotide variants identified in genome-wide association studies (GWASs), can help distinguish individuals at a high genetic risk for Alzheimer disease (AD). However, genetic studies have predominantly focused on populations of European ancestry. Objective To evaluate the transferability of a PRS for AD in the Korean population using summary statistics from a prior GWAS of European populations. Design, Setting, and Participants This cohort study developed a PRS based on the summary statistics of a large-scale GWAS of a European population (the International Genomics of Alzheimer Project; 21 982 AD cases and 41 944 controls). This PRS was tested for an association with AD dementia and its related phenotypes in 1634 Korean individuals, who were recruited from 2013 to 2019. The association of a PRS based on a GWAS of a Japanese population (the National Center for Geriatrics and Gerontology; 3962 AD cases and 4074 controls) and a transancestry meta-analysis of European and Japanese GWASs was also evaluated. Data were analyzed from December 2020 to June 2021. Main Outcomes and Measures Risk of AD dementia, amnestic mild cognitive impairment (aMCI), earlier symptom onset, and amyloid β deposition (Aβ). Results A total of 1634 Korean patients (969 women [59.3%]), including 716 individuals (43.6%) with AD dementia, 222 (13.6%) with aMCI, and 699 (42.8%) cognitively unimpaired controls, were analyzed in this study. The mean (SD) age of the participants was 71.6 (9.0) years. Higher PRS was associated with a higher risk of AD dementia independent of APOE ɛ4 status in the Korean population (OR, 1.95; 95% CI, 1.40-2.72; P &amp;amp;lt; .001). Furthermore, PRS was associated with aMCI, earlier symptom onset, and Aβ deposition independent of APOE ɛ4 status. The PRS based on a transancestry meta-analysis of data sets comprising 2 distinct ancestries showed a slightly improved accuracy. Conclusions and Relevance In this cohort study, a PRS derived from a European GWAS identified individuals at a high risk for AD dementia in the Korean population. These findings emphasize the transancestry transferability and clinical value of PRSs and suggest the importance of enriching diversity in genetic studies of AD.
Continuous Kidney Replacement Therapy Practices in Pediatric Intensive Care Units Across Europe
Authors: Marco Daverio, Gerard Cortina, Andrew Jones, Zaccaria Ricci, Demet Demirkol, Paulien Raymakers-Janssen, Francois Lion, Cristina Camilo, Vesna Stojanovic, Serge Grazioli, Tomas Zaoral, Katja Masjosthusmann, Inge Vankessel, Akash Deep, Sue Taylor, Emma Alexander, Kate Peace, Angela Amigoni, Felix Neunhoeffer
Journal: JAMA Network Open (2022)

Continuous kidney replacement therapy (CKRT) is the preferred method of kidney support for children with critical illness in pediatric intensive care units (PICUs). However, there are no data on the current CKRT management practices in European PICUs.To describe current CKRT practices across European PICUs.This cross-sectional survey of PICUs in 20 European countries was conducted by the Critical Care Nephrology Section of the European Society of Pediatric and Neonatal Intensive Care from April 1, 2020, to May 31, 2022. Participants included intensivists and nurses working in European PICUs. The survey was developed in English and distributed using SurveyMonkey. One response from each PICU that provided CKRT was included in the analysis. Data were analyzed from June 1 to June 30, 2022.Demographic characteristics of European PICUs along with organizational and delivery aspects of CKRT (including prescription, liberation from CKRT, and training and education) were assessed.Of 283 survey responses received, 161 were included in the analysis (response rate, 76%). The attending PICU consultant (70%) and the PICU team (77%) were mainly responsible for CKRT prescription, whereas the PICU nurses were responsible for circuit setup (49%) and bedside machine running (67%). Sixty-one percent of permanent nurses received training to use CKRT, with no need for certification or recertification in 36% of PICUs. Continuous venovenous hemodiafiltration was the preferred dialytic modality (51%). Circuit priming was performed with normal saline (67%) and blood priming in children weighing less than 10 kg (56%). Median (IQR) CKRT dose was 35 (30-50) mL/kg/h in neonates and 30 (30-40) mL/kg/h in children aged 1 month to 18 years. Forty-one percent of PICUs used regional unfractionated heparin infusion, whereas 35% used citrate-based regional anticoagulation. Filters were changed for filter clotting (53%) and increased transmembrane pressure (47%). For routine circuit changes, 72 hours was the cutoff in 62% of PICUs. Some PICUs (34%) monitored fluid removal goals every 4 hours, with variation from 12 hours (17%) to 24 hours (13%). Fluid removal goals ranged from 1 to 3 mL/kg/h. Liberation from CKRT was performed with a diuretic bolus followed by an infusion (32%) or a diuretic bolus alone (19%).This survey study found a wide variation in current CKRT practice, including organizational aspects, education and training, prescription, and liberation from CKRT, in European PICUs. This finding calls for concerted efforts on the part of the pediatric critical care and nephrology communities to streamline CKRT education and training, research, and guidelines to reduce variation in practice.
Association Between Attention-Deficit/Hyperactivity Disorder and Benzodiazepines and Z-Hypnotics in Pregnancy—Questions Remain
Authors: Elizabeth A. Suarez, Greta A. Bushnell
Journal: JAMA Network Open (2022)

Lene Maria Sundbakk, MSc; Jon Michael Gran, PhD; Mollie E. Wood, PhD; Marte Handal, PhD; Svetlana Skurtveit, PhD; Hedvig Nordeng, PhD
The Prevalence of Obesity Among Children With Type 2 Diabetes
Authors: Milena Cioana, Jiawen Deng, Ajantha Nadarajah, Maggie Hou, Yuan Qiu, Sondra Song Jie Chen, Angelica Rivas, Laura Banfield, Parm Pal Toor, Fangwen Zhou, Ayla Guven, Haifa Alfaraidi, Ahlam Alotaibi, Lehana Thabane, M. Constantine Samaan
Journal: JAMA Network Open (2022)

Importance The childhood obesity epidemic is presumed to drive pediatric type 2 diabetes (T2D); however, the global scale of obesity in children with T2D is unknown. Objectives To evaluate the global prevalence of obesity in pediatric T2D, examine the association of sex and race with obesity risk, and assess the association of obesity with glycemic control and dyslipidemia. Data Sources MEDLINE, Embase, CINAHL, Cochrane Library, and Web of Science were searched from database inception to June 16, 2022. Study Selection Observational studies with at least 10 participants reporting the prevalence of obesity in patients with pediatric T2D were included. Data Extraction and Synthesis Following the Meta-analysis of Observational Studies in Epidemiology reporting guideline, 2 independent reviewers in teams performed data extraction and risk of bias and level of evidence analyses. The meta-analysis was conducted using a random-effects model. Main Outcomes and Measures The primary outcomes included the pooled prevalence rates of obesity in children with T2D. The secondary outcomes assessed pooled prevalence rates by sex and race and associations between obesity and glycemic control and dyslipidemia. Results Of 57 articles included in the systematic review, 53 articles, with 8942 participants, were included in the meta-analysis. The overall prevalence of obesity among pediatric patients with T2D was 75.27% (95% CI, 70.47%-79.78%), and the prevalence of obesity at diabetes diagnosis among 4688 participants was 77.24% (95% CI, 70.55%-83.34%). While male participants had higher odds of obesity than female participants (odds ratio, 2.10; 95% CI, 1.33-3.31), Asian participants had the lowest prevalence of obesity (64.50%; 95% CI, 53.28%-74.99%), and White participants had the highest prevalence of obesity (89.86%; 95% CI, 71.50%-99.74%) compared with other racial groups. High heterogeneity across studies and varying degrees of glycemic control and dyslipidemia were noted. Conclusions and Relevance The findings of this systematic review and meta-analysis suggest that obesity is not a universal phenotype in children with T2D. Further studies are needed to consider the role of obesity and other mechanisms in diabetes genesis in this population.
Promise and perils of Canada’s new action plan to end gender based violence
Authors: Janice Du Mont, C Emma Kelly
Journal: BMJ (2022)

Canadian governments-federal, provincial, territorial, and municipal-have their work cut out after the release of Canada's National Action Plan to End Gender Based Violence last month. 1Gender based violence is defined as violence on account of "sex, gender, gender identity, gender expression, or perceived gender." 1 The action plan, which is intersectional and wide ranging in scope, presents a challenge to the systems that have long sidelined gender based violence, treating it in isolation or delegating responsibility to overburdened, underfunded community services and advocates.Women's Shelters Canada, a national non-profit organisation dedicated to ending gender based violence through advocacy, resource sharing, and research, has repeatedly called for a national action plan.Last year it was consulted by Women and Gender Equality Canada (WAGE) and worked with a multisectoral, pan-Canadian coalition of anti-violence leaders to develop a strategic roadmap. 2 That document highlighted the needs of the most marginalised victims of gender based violence and emphasised that such violence affects every facet of our society.Therefore, it is relevant not only to federal government departments such as WAGE but also to government services responsible for immigration, labour, housing, criminal justice, health, and more.
Rates of Hypoglycemic and Hyperglycemic Emergencies Among U.S. Adults With Diabetes, 2011–2020
Authors: Rozalina G. McCoy, Jeph Herrin, Rodolfo J. Galindo, Kavya Sindhu Swarna, Guillermo E. Umpierrez, Sherita Hill Golden, Patrick J. O’Connor
Journal: Diabetes Care (2022)
Prevalence of SARS-CoV-2 and Influenza Coinfection and Clinical Characteristics Among Children and Adolescents Aged &lt;18 Years Who Were Hospitalized or Died with Influenza — United States, 2021–22 Influenza Season
Authors: Katherine Adams, Katie J. Tastad, Stacy Huang, Dawud Ujamaa, Krista Kniss, Charisse Cummings, Arthur Reingold, Jeremy Roland, Elizabeth Austin, Breanna Kawasaki, James Meek, Kimberly Yousey-Hindes, Evan J. Anderson, Kyle P. Openo, Libby Reeg, Lauren Leegwater, Melissa McMahon, Erica Bye, Mayvilynne Poblete, Zachary Landis, Nancy L. Spina, Kerianne Engesser, Nancy M. Bennett, Maria A. Gaitan, Eli Shiltz, Nancy Moran, Melissa Sutton, Nasreen Abdullah, William Schaffner, H. Keipp Talbot, Kristen Olsen, Holly Staten, Christopher A. Taylor, Fiona P. Havers, Carrie Reed, Alicia Budd, Shikha Garg, Alissa O’Halloran, Lynnette Brammer
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

The 2022-23 influenza season shows an early rise in pediatric influenza-associated hospitalizations (1). SARS-CoV-2 viruses also continue to circulate (2). The current influenza season is the first with substantial co-circulation of influenza viruses and SARS-CoV-2 (3). Although both seasonal influenza viruses and SARS-CoV-2 can contribute to substantial pediatric morbidity (3-5), whether coinfection increases disease severity compared with that associated with infection with one virus alone is unknown. This report describes characteristics and prevalence of laboratory-confirmed influenza virus and SARS-CoV-2 coinfections among patients aged <18 years who had been hospitalized or died with influenza as reported to three CDC surveillance platforms during the 2021-22 influenza season. Data from two Respiratory Virus Hospitalizations Surveillance Network (RESP-NET) platforms (October 1, 2021-April 30, 2022),
<i>QuickStats:</i> Birth Rates* for Females Aged 15–19 Years, by State — National Vital Statistics System, United States, 2021
Authors: Brady Hamilton
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

DC 13.0-19.98.0-12.95.4-7.920.0-26.5 * Births per 1,000 females aged 15-19 years.In 2021, the U.S. birth rate for females aged 15-19 years was 13.9 births per 1,000 persons, with rates generally lower in the Northeast and higher across the southern states.Birth rates among females aged 15-19 years ranged from 5.4 in New Hampshire, 5.7 in Massachusetts, and 6.4 in Vermont to 26.5 in Arkansas and 25.6 in Mississippi.
<i>Notes from the Field: Burkholderia pseudomallei</i> Detected in a Raccoon Carcass Linked to a Multistate Aromatherapy-Associated Melioidosis Outbreak — Texas, 2022
Authors: Julia K. Petras, Mindy G. Elrod, Maureen Ty, Pratistha Adams, Dan Zahner, Adam Adams, M. Worth Calfee, Christine Tomlinson, Shannon Serre, Shawn Ryan, Elise Jakabhazy, Jay E. Gee, Zachary Weiner, William A. Bower, Maria E. Negron, Alex R. Hoffmaster, Heidi Honza
Journal: MMWR Morbidity and Mortality Weekly Report (2022)
G-quadruplexes sense natural porphyrin metabolites for regulation of gene transcription and chromatin landscapes
Authors: Conghui Li, Zhinang Yin, Ruijing Xiao, Beili Huang, Yali Cui, Honghong Wang, Ying Xiang, Lingrui Wang, Lingyu Lei, Jiaqin Ye, Tianyu Li, Youquan Zhong, Fangteng Guo, Yuchen Xia, Pingping Fang, Kaiwei Liang
Journal: Genome biology (2022)

G-quadruplexes (G4s) are unique noncanonical nucleic acid secondary structures, which have been proposed to physically interact with transcription factors and chromatin remodelers to regulate cell type-specific transcriptome and shape chromatin landscapes.
Retraction Note: α-santalol inhibits the angiogenesis and growth of human prostate tumor growth by targeting vascular endothelial growth factor receptor 2-mediated AKT/mTOR/P70S6K signaling pathway
Authors: Sarita Saraswati, Shakti Kumar, Abdulqader A. Alhaider
Journal: Molecular Cancer (2022)

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/1476-4598-12-147.
Strobealign: flexible seed size enables ultra-fast and accurate read alignment
Authors: Kristoffer Sahlin
Journal: Genome biology (2022)

Read alignment is often the computational bottleneck in analyses. Recently, several advances have been made on seeding methods for fast sequence comparison. We combine two such methods, syncmers and strobemers, in a novel seeding approach for constructing dynamic-sized fuzzy seeds and implement the method in a short-read aligner, strobealign. The seeding is fast to construct and effectively reduces repetitiveness in the seeding step, as shown using a novel metric E-hits. strobealign is several times faster than traditional aligners at similar and sometimes higher accuracy while being both faster and more accurate than more recently proposed aligners for short reads of lengths 150nt and longer. Availability: https://github.com/ksahlin/strobealign.
Human CD19-specific switchable CAR T-cells are efficacious as constitutively active CAR T-cells but cause less morbidity in a mouse model of human CD19<sup>+</sup>malignancy
Authors: Christopher A Pennell, Heather Campbell, Meghan D Storlie, Sara Bolivar-Wagers, Mark J Osborn, Yosef Refaeli, Michael Jensen, Sophie Viaud, Travis S Young, Bruce R Blazar
Journal: Journal for ImmunoTherapy of Cancer (2022)

Current Food and Drug Administration (FDA)-approved CD19-specific chimeric antigen receptor (CAR) T-cell therapies for B-cell malignancies are constitutively active and while efficacious, can cause morbidity and mortality. Their toxicities might be reduced if CAR T-cell activity was regulatable rather than constitutive. To test this, we compared the efficacies and morbidities of constitutively active (conventional) and regulatable (switchable) CAR (sCAR) T-cells specific for human CD19 (huCD19) in an immune-competent huCD19 + transgenic mouse model. Conventional CAR (CAR19) and sCAR T-cells were generated by retrovirally transducing C57BL/6 (B6) congenic T-cells with constructs encoding antibody-derived single chain Fv (sFv) fragments specific for huCD19 or a peptide neoepitope (PNE), respectively. Transduced T-cells were adoptively transferred into huCD19 transgenic hemizygous ( huCD19 Tg/0 ) B6 mice; healthy B-cells in these mice expressed huCD19 Tg . Prior to transfer, recipients were treated with a lymphodepleting dose of cyclophosphamide to enhance T-cell engraftment. In tumor therapy experiments, CAR19 or sCAR T-cells were adoptively transferred into huCD19 Tg/0 mice bearing a syngeneic B-cell lymphoma engineered to express huCD19. To regulate sCAR T cell function, a switch protein was generated that contained the sCAR-specific PNE genetically fused to an anti-huCD19 Fab fragment. Recipients of sCAR T-cells were injected with the switch to link sCAR effector with huCD19 + target cells. Mice were monitored for survival, tumor burden (where appropriate), morbidity (as measured by weight loss and clinical scores), and peripheral blood lymphocyte frequency. CAR19 and sCAR T-cells functioned comparably regarding in vivo expansion and B-cell depletion. However, sCAR T-cells were better tolerated as evidenced by the recipients’ enhanced survival, reduced weight loss, and improved clinical scores. Discontinuing switch administration allowed healthy B-cell frequencies to return to pretreatment levels. In our mouse model, sCAR T-cells killed huCD19 + healthy and malignant B-cells and were better tolerated than CAR19 cells. Our data suggest sCAR might be clinically superior to the current FDA-approved therapies for B-cell lymphomas due to the reduced acute and chronic morbidities and mortality, lower incidence and severity of side effects, and B-cell reconstitution on cessation of switch administration.
Targeted CuFe2O4 hybrid nanoradiosensitizers for synchronous chemoradiotherapy
Authors: Marziyeh Salehiabar, Mohammadreza Ghaffarlou, Ali Mohammadi, Navid Mousazadeh, Hossein Rahimi, Fatemeh Abhari, Hamid Rashidzadeh, Leila Nasehi, Hamed Rezaeejam, Murat Barsbay, Yavuz Nuri Ertas, Hamed Nosrati, Taras Kavetskyy, Hossein Danafar
Journal: Journal of Controlled Release (2022)
Yap governs a lineage-specific neuregulin1 pathway-driven adaptive resistance to RAF kinase inhibitors
Authors: Maria E. R. Garcia-Rendueles, Gnana Krishnamoorthy, Mahesh Saqcena, Adrian Acuña-Ruiz, Giovanna Revilla, Elisa de Stanchina, Jeffrey A. Knauf, Rona Lester, Bin Xu, Ronald A. Ghossein, James A. Fagin
Journal: Molecular Cancer (2022)

Inactivation of the Hippo pathway promotes Yap nuclear translocation, enabling execution of a transcriptional program that induces tissue growth. Genetic lesions of Hippo intermediates only identify a minority of cancers with illegitimate YAP activation. Yap has been implicated in resistance to targeted therapies, but the mechanisms by which YAP may impact adaptive resistance to MAPK inhibitors are unknown.We screened 52 thyroid cancer cell lines for illegitimate nuclear YAP localization by immunofluorescence and fractionation of cell lysates. We engineered a doxycycline (dox)-inducible thyroid-specific mouse model expressing constitutively nuclear YAPS127A, alone or in combination with endogenous expression of either HrasG12V or BrafV600E. We also generated cell lines expressing dox-inducible sh-miR-E-YAP and/or YAPS127A. We used cell viability, invasion assays, immunofluorescence, Western blotting, qRT-PCRs, flow cytometry and cell sorting, high-throughput bulk RNA sequencing and in vivo tumorigenesis to investigate YAP dependency and response of BRAF-mutant cells to vemurafenib.We found that 27/52 thyroid cancer cell lines had constitutively aberrant YAP nuclear localization when cultured at high density (NU-YAP), which rendered them dependent on YAP for viability, invasiveness and sensitivity to the YAP-TEAD complex inhibitor verteporfin, whereas cells with confluency-driven nuclear exclusion of YAP (CYT-YAP) were not. Treatment of BRAF-mutant thyroid cancer cells with RAF kinase inhibitors resulted in YAP nuclear translocation and activation of its transcriptional output. Resistance to vemurafenib in BRAF-mutant thyroid cells was driven by YAP-dependent NRG1, HER2 and HER3 activation across all isogenic human and mouse thyroid cell lines tested, which was abrogated by silencing YAP and relieved by pan-HER kinase inhibitors. YAP activation induced analogous changes in BRAF melanoma, but not colorectal cells.YAP activation in thyroid cancer generates a dependency on this transcription factor. YAP governs adaptive resistance to RAF kinase inhibitors and induces a gene expression program in BRAFV600E-mutant cells encompassing effectors in the NRG1 signaling pathway, which play a central role in the insensitivity to MAPK inhibitors in a lineage-dependent manner. HIPPO pathway inactivation serves as a lineage-dependent rheostat controlling the magnitude of the adaptive relief of feedback responses to MAPK inhibitors in BRAF-V600E cancers.